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A comprehensive toxicity evaluation of novel amino acid-modified magnetic ferrofluids for magnetic resonance imaging

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Abstract

Stem cells have been widely exploited as remedial agents in regenerative medicine due to its tremendous potential in treatment of various debilitating diseases. In spite of this fact, there is need of a reliable, clinically applicable cell tracker for deciphering the homing and distribution of stem cells post-transplantation. Researchers have proposed the use of superparamagnetic magnetite (Fe3O4) nanoparticles for in vivo and in vitro tracking and imaging of stem cells. However, there is not much understanding of the chemical coatings on the nanoparticles, which is very important for the sustainability of stem cells in biological system. For any biomedical applications, the surface properties and the core structure of nanoparticles play a significant role. This study reports surface modification of magnetic Fe3O4 nanofluid with biocompatible amino acids viz., arginine and histidine to maintain colloidal stability at neutral pH, impart least disruption when encountered with the biological system and allow labeling with mesenchymal stem cells (MSCs). The size of amino acids-modified magnetic nanoferrofluid (AA@MNFs) was restricted to 15–25 nm for enhanced uptake in stem cells. In vitro cytotoxicity profile of stem cells labeled AA@MNFs was estimated using various assays like MTT, LDH and AO/EtBr followed by detailed pre-clinical toxicity assessment of AA@MNFs which illustrated least toxicity effects in major tissues of the animals. In vitro MRI scans of the stem cells labeled AA@MNFs confirmed the suitability of the reported ferrofluids for the use as MR contrast agents.

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Acknowledgements

The authors would like to acknowledge Department of MEMS, IIT Bombay for VSM analysis, Dr. K. C. Barick, Bhabha Atomic Research Centre (BARC) for XRD facility and Dr. Kolja Them, University Medical Center, Hamburg for TEM analysis. The authors would also like to acknowledge Department of Biosciences and Bioengineering (BSBE), IIT Bombay for confocal microscopy facility. We would also like to acknowledge Dr. Bhawan Paunipagar, Head Radiologist, Wockhardt Hospitals, Mumbai and Mr. Thomas Kurian, Philps International, Mumbai for their help with MRI studies.

Funding

The authors would like to thank Department of Biotechnology (DBT), Govt of India, for financial support under the Grant No: BT/PR21753/MED/31/355/2016. Ms. Ruchita Shelat is a recipient of Women’s Scientist Scheme-A (WOS-A), Department of Science and Technology (DST), under the Grant No: SR/WOS-A/LS-453.

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Authors and Affiliations

  1. Department of Biological Sciences, Sunandan Divatia School of Science, NMIMS University, Vile Parle (West), Mumbai, 400056, India

    Ruchita Shelat & Aparna Khanna

  2. Department of Pharmacology, SVKM’s Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (West), Mumbai, 400056, India

    Lokesh Kumar Bhatt

  3. Department of Chemistry, Sunandan Divatia School of Science, NMIMS University, Vile Parle (West), Mumbai, 400056, India

    Sudeshna Chandra

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  1. Ruchita Shelat
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Correspondence to Sudeshna Chandra.

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All applicable national (CPCSEA) and institutional guidelines (IAEC) for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the NMIMS institution.

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Shelat, R., Bhatt, L.K., Khanna, A. et al. A comprehensive toxicity evaluation of novel amino acid-modified magnetic ferrofluids for magnetic resonance imaging. Amino Acids 51, 929–943 (2019). https://doi.org/10.1007/s00726-019-02726-1

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